Development of a PLGA nanoparticle drug delivery system containing imaging/hyperthermia and chemotherapy agents

Nanoparticulate drug delivery systems have the potential to allow delivery of diagnostic and therapeutic agents to tumor sites in a targeted manner. The objective of this study was to develop biodegradable poly(DL-lactide-co-glycolic acid) (PLGA) nanoparticles loaded with an imaging/hyperthermia agent and a chemotherapy agent to allow for simultaneous diagnostics and treatment. Indocyanine Green (ICG) was selected as the imaging/hyperthermia agent, and doxorubicin (DOX) as the chemotherapy agent. The modified oil in water emulsion solvent evaporation method was used for PLGA nanoparticle preparation. To achieve an optimal degree of incorporation and particle size, we systematically assessed four independent processing variables including amount of PLGA, initial ICG amount, initial DOX amount, and PVA concentration. For every combination, we measured the nanoparticle size and the percent entrapment of ICG and DOX into the PLGA nanoparticles. The nanoparticles produced by optimal formulation had sizes of 171± 2 nm, (n=3) with a low polydispersity index (0.040 ± 0.014, n=3). We determined the entrapment efficiency (by fluorescence measurements using DMSO burst release) as 44.4 ± 1.6 % for ICG and 74.3 ± 1.9 % for DOX. Drug loading was 0.015 ± 0.001 % w/w for ICG and 0.022 ± 0.001% w/w for DOX (n=3). The release pattern was biphasic.